Mitochondrial 2-oxoglutarate/malate carrier protein

SLC25A11 encodes the mitochondrial 2-oxoglutarate/malate carrier protein (OGCP), which catalyzes electroneutral exchange of 2-oxoglutarate for malate and other dicarboxylic acids across the inner mitochondrial membrane (UniProt: Q02978). This transporter supports critical metabolic pathways including the malate-aspartate shuttle, gluconeogenesis, and nitrogen metabolism, and also regulates mitochondrial morphology and apoptosis.

SLC25A11 is primarily expressed in mitochondria-rich tissues and mutations are associated with pheochromocytoma/paraganglioma syndrome 6 (UniProt: Q02978). The protein's role in maintaining mitochondrial cristae organization and metabolic homeostasis positions it within broader cellular energy and redox regulation networks.

In Alzheimer's disease, SLC25A11 is downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC: −0.304; Chaparral AD proteomics). This reduction may impair mitochondrial metabolic coupling and energy production, processes increasingly recognized as compromised in AD pathogenesis. Whether this reflects a primary pathological event or secondary consequence requires further investigation.